Exome sequencing identifies frequent mutation of ARID1A in molecular subtypes of gastric cancer

Gastric cancer is a heterogeneous disease with multiple environmental etiologies and alternative pathways of carcinogenesis. Beyond mutations in TP53, alterations in other genes or pathways account for only small subsets of the disease. We performed exome sequencing of 22 gastric cancer samples and identified previously unreported mutated genes and pathway alterations; in particular, we found genes involved in chromatin modification to be commonly mutated. A downstream validation study confirmed frequent inactivating mutations or protein deficiency of ARID1A, which encodes a member of the SWI-SNF chromatin remodeling family, in 83% of gastric cancers with microsatellite instability (MSI), 73% of those with Epstein-Barr virus (EBV) infection and 11% of those that were not infected with EBV and microsatellite stable (MSS). The mutation spectrum for ARID1A differs between molecular subtypes of gastric cancer, and mutation prevalence is negatively associated with mutations in TP53. Clinically, ARID1A alterations were associated with better prognosis in a stage-independent manner. These results reveal the genomic landscape, and highlight the importance of chromatin remodeling, in the molecular taxonomy of gastric cancer.     

Epigenetic identification of receptor tyrosine kinase-like orphan receptor 2 as a functional tumor suppressor inhibiting β-catenin and AKT signaling but frequently methylated in common carcinomas

Through subtraction of tumor-specific CpG methylation, we identified receptor tyrosine kinase-like orphan receptor 2 (ROR2) as a candidate tumor suppressor gene (TSG). ROR2 is a specific receptor or co-receptor for WNT5A, involved in canonical and non-canonical WNT signaling, with its role in tumorigenesis controversial. We characterized its functions and related cell signaling in common carcinomas. ROR2 was frequently silenced by promoter CpG methylation in multiple carcinomas including nasopharyngeal, esophageal, gastric, colorectal, hepatocellular, lung, and breast cancers, while no direct correlation of ROR2 and WNT5A expression was observed. Ectopic expression of ROR2 resulted in tumor suppression independent of WNT5A status, through inhibiting tumor cell growth and inducing cell cycle arrest and apoptosis. ROR2 further suppressed epithelial-mesenchymal transition and tumor cell stemness through repressing β-catenin and AKT signaling, leading to further inhibition of tumor cell migration/invasion and increased chemo-sensitivity. Thus ROR2, as an epigenetically inactivated TSG, antagonizes both β-catenin and AKT signaling in multiple tumorigenesis. Its epigenetic silencing could be a potential tumor biomarker and therapeutic target for carcinomas.     

Influenza infection induces host DNA damage and dynamic DNA damage responses during tissue regeneration

Influenza viruses account for significant morbidity worldwide. Inflammatory responses, including excessive generation of reactive oxygen and nitrogen species (RONS), mediate lung injury in severe influenza infections. However, the molecular basis of inflammation-induced lung damage is not fully understood. Here, we studied influenza H1N1 infected cells in vitro, as well as H1N1 infected mice, and we monitored molecular and cellular responses over the course of 2 weeks in vivo. We show that influenza induces DNA damage to both, when cells are directly exposed to virus in vitro (measured using the comet assay) and also when cells are exposed to virus in vivo (estimated via γH2AX foci). We show that DNA damage, as well as responses to DNA damage persist in vivo until long after virus has been cleared, at times when there are inflammation associated RONS (measured by xanthine oxidase activity and oxidative products). The frequency of lung epithelial and immune cells with increased γH2AX foci is elevated in vivo, especially for dividing cells (Ki-67-positive) exposed to oxidative stress during tissue regeneration. Additionally, we observed a significant increase in apoptotic cells as well as increased levels of DNA double strand break (DSB) repair proteins Ku70, Ku86 and Rad51 during the regenerative phase. In conclusion, results show that influenza induces DNA damage both in vitro and in vivo, and that DNA damage responses are activated, raising the possibility that DNA repair capacity may be a determining factor for tissue recovery and disease outcome.     

基于AlN压电层的薄膜体声波谐振器

以AlN薄膜为压电层,采用体硅微细加工工艺制备背空腔型结构薄膜体声波谐振器.材料测试结果表明,在优化溅射工艺下沉积的AlN薄膜具有(002)择优取向及良好的柱状晶结构.扫描电镜表征结果证实所制得空腔背部平滑且各向异性较好.用网络分析仪测试可知,所制得的谐振器具有较好的频率特性:谐振频率为2.537 GHz,机电耦合系数3.75%,串、并联品质因数分别为101.8、79.7.     

多重PCR法快速鉴定转基因小麦植株及后代

根据转基因植物中常用的报告基因uidA、选择基因bar的序列,设计合成两对不同的引物,建立了在转基因小麦材料分子确证中,应用一次PCR反应同时扩增检测两种或多种外源基因的多重PCR方法．通过对质粒pAHC25以及30个转基因小麦样品进行PCR扩增分析,比较多重PCR的检测结果与单基因的PCR扩增结果,发现两者结果完全一致．     

Deep Web爬虫研究与设计

随着Web的发展,越来越多的数据可以通过表单提交来获取,这些表单提交所产生信息是由Deep Web后台数据库动态产生的.在这种情况下,信息集成就更加需要Web爬虫来自动获取这些页面以进一步地处理数据.为了帮助用户完成这样的任务,提出一种用于搜集Deep Web页面的爬虫的设计方法.此方法使用一个预定义的领域本体知识库来识别这些页面的内容,同时利用一些来自Web站点的导航模式来识别自动填写表单时所需进行的路径导航.通过对来自不同领域的Deep Web站点的大量实验,验证了此方法是非常有效的.     

一种改进的iTrace技术的研究

针对现有ICMP反向追踪方法中iTrace信息标记的IP地址或相关信息,导致重构完整攻击路径需要过多的数据包,并且计算量大的问题,提出了在iTrace分组中重新编码的方案。该方案可在较短的时间内推算出主要攻击路径,显著减少路径重构时对数据包的需求量,从而可以使受害者更快捷地追踪到攻击源,为受害者尽快响应攻击、减少攻击带来的损失创造了条件。     

CVD金刚石涂层刀具附着力的研究

以压痕法涂层破碎时的负荷来评估附着力,采用稀盐酸对衬底进行表面处理,在ＣＶＤ沉积过程中添加适量粘结促进剂以压抑金属钴的催化墨化作用,沉积合适的厚度,可在硬质合金衬底上得到高附着力的金刚石涂层刀具．用该刀具对含碳化硅颗粒的铝基复合材料进行切削试验,得到了满意的结果．     

酸性条件下多壁碳纳米管负载铁基催化氧化甲烷性能

寻求绿色、安全且低能耗的转化技术是实现甲烷转化和利用的关键。采用浸渍法制备了多壁碳纳米管负载铁基的复合催化剂(Fe/MWCNTs),通过比表面积测试法(Brunauer-Emmett-Teller, BET)、X射线光电子能谱技术(X-ray photoelectron spectroscopy, XPS)、X射线衍射(X-ray diffraction, XRD)、透射电子显微镜(transmission electron microscope, TEM)和傅里叶变换红外光谱仪(Fourier transform infrared spectrometer, FTIR)等技术表征了Fe/MWCNTs的结构形态,得知Fe/MWCNTs的活性催化组分主要是α-Fe_2O_3,负载后催化剂比表面积明显增大,且在碳纳米管表面形成的是活性较强的110晶面。在冰乙酸体系中建立Fe/MWCNTs催化体系催化氧化甲烷,通过气相液相产物分析计算甲烷转化率和醋酸甲酯生成量,考察反应温度、压力、时间、催化剂投加量和氧化剂浓度对甲烷催化氧化的反应效果的影响,通过正交试验得到冰乙酸体系中催化甲烷的最佳反应条件。实验表明:在反应温度90℃,反应压力为3 MPa, Fe/MWCNTs复合催化剂0.15 g,氧化剂高锰酸钾浓度为0.2 mol/L,反应时间为4 h的最佳反应条件下,甲烷转化率可达24.78%,醋酸甲酯产量为541.72×10~(-6)。     

电动舵机极限环机理分析和抑制措施

针对电动舵机结构,建立了一种考虑减速器等效刚度的舵机模型.利用描述函数法,分析了舵机在考虑传动间隙情况下诱导的极限环,进而分析了在有无舵片所受摩擦力情况下极限环的频率特性.针对该类传动非线性,提出了一种工程上可实现的负反馈力矩机制来改变舵机在间隙区间的运动模态,从而抑制极限环振荡,并且给出了负反馈系数的选取准则.最后进...